Characteristics of the test: (1 gene)
SPAST, SPG4 (OMIM #604277)
Basic characteristics of the clinical phenotype:
Hereditary spastic paraplegia (HSP) is a group of clinically and genetically heterogeneous neurodegenerative diseases with major clinical features including progressive weakness and spasticity in the lower limbs, hyperreflexia, extensor-plantar response, and a characteristic spastic-paraparetic gait. The onset of the disease can vary from infancy to adulthood.
It is due to loss of function of the pyramidal tracts due to axonal degeneration.
The most common form of the disease, SPG4 is associated with mutations in the spastin gene, SPAST. This form constitutes up to 1/3 of all forms of NSP and includes up to 60% of cases with an autosomal dominant type of inheritance and up to 15% of sporadic cases. Mutations in the SPAST gene are associated with a pure form of the disease, with or without urinary or sensory dysfunction. As additional symptoms, in 5–10% of cases, ataxia or peripheral motor involvement were found, and in less than 5%, cognitive disorders, extrapyramidal symptoms, dysarthria, or dysphagia were present.
Reasons for referring - Autosomal dominant type of inheritance, pure form of the disease. Sporadic cases.
Confirmation of diagnosis; Making a diagnosis; Determining the risk of developing the disease.
Presence of weakness and spasticity in lower limbs, hyperreflexia, extensor-plantar response, disturbances in determining position in space, characteristic spastic-paraparetic gait, pelvic reservoir disturbances, etc.
Interpretation of results:
The identification of point mutations and small deletions/insertions in the SPG4 gene will allow a genetic diagnosis of SPG4-related hereditary spastic paraplegia.
Presence of large deletions and insertions cannot be detected by this method. A combination with a suitable CNV analysis (MLPA, aCGH) is recommended for their detection.
The genetic counselor will interpret and answer all questions you may have about your result.
Method: Sanger sequencing (ABI 3130xl).
The method involves bi-directional DNA sequencing of all coding exons and intron-exon boundaries of the SPAST gene. The laboratory offers single exon sequencing in relatives of patients to determine the carrier status in cases where the mutation is known (Test #182).
Sensitivity of the method: 99.5%
What does the test involve?
- DNA isolation and sample storage.
- Direct sequencing of target genes/gene regions for detection of pathogenic mutations.
- Forming a written result of the genetic test.
- Diagnostic interpretation of results and genetic counseling.
Biological material: Venous blood or DNA
For more information, please read the "Biological material requirements and shipping information" carefully.
